The disproportionation of the hemimercaptals of glutathione and alpha-ketoaldehydes into the corresponding thiolesters of glutathione and alpha-hydroxycarboxylic acid is catalyzed intracellularly by the ubiquitous glyoxalase system which is thought by some investigators to be involved in normal and abnormal growth and development. We propose to study the comparative enzymology of glyoxalase isolated from normal and abnormal tissue in order to examine the mechanism and regulation of the enzyme in different tissues and to test whether there are isozyme changes for glyoxalase in hosts bearing a neoplasia. This possible isozyme change may be of some diagnostic value in cancer detection, quite apart from the possible regulatory role of glyoxalase. The basic methods for isolation, purification and mechanism characterization of the enzymes have been worked out in previous studies, primarily using yeast glyoxalase and bovine erythrocyte glyoxalase. Additional studies directed toward elucidating the metabolic origins and intracellular functions of alpha-ketoaldehydes are proposed, with major emphasis placed upon determining the interrelationships between alpha-ketoaldehyde metabolism and glutathione metabolism.